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J Biol Chem. 2014 Nov 7;289(45):31121-35. doi: 10.1074/jbc.M114.556290. Epub 2014 Sep 16.

Identification of 14-3-3β gene as a novel miR-152 target using a proteome-based approach.

Author information

1
From the Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle and.
2
the Institute of Molecular Medicine, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
3
From the Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle and barbara.seliger@uk-halle.de.

Abstract

Recent studies demonstrated that miR-152 overexpression down-regulates the nonclassical human leukocyte antigen (HLA) class I molecule HLA-G in human tumors thereby contributing to their immune surveillance. Using two-dimensional gel electrophoresis followed by MALDI-TOF mass spectrometry, the protein expression profile of HLA-G(+), miR-152(low) cells, and their miR-152-overexpressing (miR(high)) counterparts was compared leading to the identification of 24 differentially expressed proteins. These were categorized according to their function and localization demonstrating for most of them an important role in the initiation and progression of tumors. The novel miR-152 target 14-3-3 protein β/α/YWHAB (14-3-3β) is down-regulated upon miR-152 overexpression, although its overexpression was often found in tumors of distinct origin. The miR-152-mediated reduction of the 14-3-3β expression was accompanied by an up-regulation of BAX protein expression resulting in a pro-apoptotic phenotype. In contrast, the reconstitution of 14-3-3β expression in miR-152(high) cells increased the expression of the anti-apoptotic BCL2 gene, enhances the proliferative activity in the presence of the cytostatic drug paclitaxel, and causes resistance to apoptosis induced by this drug. By correlating clinical microarray data with the patients' outcome, a link between 14-3-3β and HLA-G expression was found, which could be associated with poor prognosis and overall survival of patients with tumors. Because miR-152 controls both the expression of 14-3-3β and HLA-G, it exerts a dual role in tumor cells by both altering the immunogenicity and the tumorigenicity.

KEYWORDS:

14-3-3β; Cell Biology; HLA-G; Immunology; MicroRNA (miRNA); Oncogene; Tumor Immunology; miR-152

PMID:
25228695
PMCID:
PMC4223316
DOI:
10.1074/jbc.M114.556290
[Indexed for MEDLINE]
Free PMC Article

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